Kakali De

Synthesis and evaluation of 99mTc-moxifloxacin, a potential infection specific imaging agent

To synthesize and evaluate a (99m)Tc labeled fluroquinolone, moxifloxacin as a potential bacteria specific infection imaging agent. A radiolabeling formulation including moxifloxacin, [Moxicip(TM) injection, Cipla] (4mg), sodium pertechnetate and stannous chloride (5microg) gave the best radiolabeling efficiency and moderately stable labeled (99m)Tc moxifloxacin. Quality control analysis was performed by ITLC. Rats and rabbit with infectious intramuscular lesions induced in either thigh with E. Colli were used for studying biodistribution and scintigraphic imaging of the labeled product. Imaging of an infected thigh of a rabbit was performed with a gamma-camera at various intervals. A good radiolabeling efficiency (90-95%) was obtained within 5min. No purification of the labeled product was done. Labeled product retained its radiochemical purity upto 85% even at 3h. Scintigraphy showed uptake in infectious lesions at 30min after injection, which remains constant upto 3h study. Abscess-to-muscle ratios were 1.60, 1.62, 1.74 and 1.75 at 30min, 1, 2 and 3h, respectively. Thus, (99m)Tc moxifloxacin, a new potential radiopharmaceutical has been developed for infection imaging agent.

Preparation and evaluation of 99mTc-cefuroxime, a potential infection specific imaging agent: a reliable thin layer chromatographic system to delineate impurities from the 99mTc-antibiotic.

Technetium-99m labelled cefuroxime, a second-generation cephalosporin antibiotic and potential bacteria specific infection imaging agent was evaluated. A good radiochemical purity (95%) of the labelled product was obtained after filtering the reaction mixture through a 0.22 μm filter. Scintigraphy study of the purified product showed uptake in infectious lesions 45 min after injection and abscess-to-muscle ratios were found to be 1.80, 1.85 and 1.88 at 45 min, 1.5 hr and 3 hr, respectively. A versatile and reliable chromatographic technique to assess the radiochemical purity of (99m)Tc-cefuroxime has also been described.

Polymers derived from Xanthomonas campesteris and Cyamopsis tetragonolobus used as retardant materials for the formulation of sustained release floating matrix tablet of atenolol

The objective of the present study was to develop, optimize, in vitro, and in vivo evaluation of floating matrix tablet of atenolol using polymer blend derived from Xanthomonas campesteris and Cyamopsis tetragonolobus that are characterized by release requirements of sustained-release product and to improve the oral bioavailability of the drug. A 3(2) full factorial design was employed to optimize the tablets, where content of polymer blend (X1) and ratio of xanthan gum-to-guar gum (X2) were considered as independent variables. The effects of independent variables on dependent variables, i.e. floating time, diffusion exponent, and time to release 50% of atenolol were evaluated. The in vivo pharmacokinetic parameters of the optimized formulation were compared with the marketed sustained release formulation of atenolol (Aten(®)). The optimized formulation containing 20% (w/w) of polymer blend and 50:50 ratio of xanthan gum-to-guar gum was able to float more than 12h and showed the desired sustained drug release from the tablets. In vivo retention studies in rabbit stomach showed the gastric residence of tablet up to 6h. The in vivo study of optimized tablets illustrated significant improvement in the oral bioavailability of atenolol in rabbits. It can be concluded that floating matrix tablet of atenolol prepared by using xanthan gum and guar gum has potential for sustained release of the drug as well as improved oral bioavailability through enhanced gastric residence time of formulation in stomach.

Assessment of the effect of Bacopa monnieri (L.) Wettst. extract on the labeling of blood elements with technetium-99m and on the morphology of red blood cells

Bacopa monnieri (L.) Wettst. (BM), a traditional Ayurvedic medicine, used for centuries as a memory enhancing, anti-inflammatory, antipyretic, sedative and antiepileptic agent. BM extract have been extensively investigated by several authors for their neuropharmacological effects. In nuclear medicine, red blood cells (RBC) labeled with technetium-99m (99mTc) have several clinical applications. However, data have demonstrated that synthetic or natural drugs could modify the labeling of RBC with 99mTc. As Bacopa monnieri is extensively used in medicine, we evaluated its influence on the labeling of RBC and plasma proteins using technetium-99m (99mTc). This labeling procedure depends on a reducing agent and usually stannous chloride is used. Blood was incubated with BM extracts. Stannous chloride solution and 99mTc were added. Blood was centrifuged and plasma (P) and blood cells (BC) were isolated. Samples of P or BC were also precipitated, centrifuged and insoluble fraction (IF) and soluble fraction (SF) were separated. The percentage of radioactivity (%ATI) in BC, IF-BC and IF-P were calculated. The %ATI significantly decreased on BC from 95.53±0.45 to 35.41±0.44, on IF-P from 80.20±1.16 to 7.40±0.69 and on IF-BC from 73.31±1.76 to 21.26±1.40. The morphology study of RBC revealed important morphological alterations due to treatment with BM extracts. We suggest that the BM extract effect could be explained by an inhibition of the stannous and pertechnetate ions or oxidation of the stannous ion or by damages induced in the plasma membrane.

Synthesis, radiolabeling and biological evaluation of a neutral tripeptide and its derivatives for potential nuclear medicine applications

Peptides are important regulators of growth and cellular functions not only in normal tissue but also in tumors. So they are becoming radioligands of increasing interest in nuclear oncology for targeted tumor diagnosis and therapy. So development of new peptide radiopharmaceuticals is becoming one of the most important areas in nuclear medicine research. A small tripeptide derivative NH(2)PhePheCys was synthesized by Fmoc solid phase peptide synthesis using an automated synthesizer. The oxidized form, i.e. NH(2)PhePheCysCysPhePheNH(2,) was also prepared by iodine oxidation method from NH(2)PhePheCys(ACM). The ligands were analyzed by HPLC and mass spectroscopy. They were radiolabeled with (99m)Tc using SnCl(2). In vitro analytical studies and biological characterizations were performed using the peptide radiopharmaceuticals. Images taken under gamma camera showed very high uptake in the liver, lung and spleen. Significant uptake was also observed in bone marrow and brain for (99m)Tc-NH(2)PhePheCys. Metabolites were produced in vivo when the radiopharmaceuticals were injected intravenously and were identified from rat brain and liver homogenate studies. Clearance through kidney did not show any evidence of breaking of the labeled compounds and formation of free (99m)Tc. Radiopharmaceuticals prepared using tripeptide and hexapeptide ligands were transported into the brain through blood brain barrier depending on the size and sequence characteristics. Using this property of peptide new derivatives can be prepared to develop (99m)Tc radiopharmaceuticals for imaging normal brain tissues as well as for diagnosing various brain disorders.

Synthesis and Exploration of Novel Radiolabeled Bombesin Peptides for Targeting Receptor Positive Tumor.

Graphical abstract Figure. No Caption available. HighlightsSynthesis and biological interpretation of two new bombesin analogs HYNIC‐Asp[Phe13]BBN(7–13)‐NH‐CH2‐CH2‐CH3 (BA1) and HYNIC‐Pro[Tyr13,Met14]BBN‐ (7–14)‐NH2 (BA2) were synthesized and compared to BBN(7–14)‐NH2 (BS) with the goal of improving GRP receptor specific cellular internalization and retention of radioactivity in cancer cells for targeting molecular imaging.These BBN peptides could efficiently be radiolabeled with 99mTc via the ligand exchange method which exhibited improved radiochemical and in vitro metabolic stability compared to the previously reported analogs BS.Binding assay of radioconjugates confirmed its high binding affinity (affinity sequences were BA1 > BA2 > BS) towards GRP receptor specific breast cancer cell line MDA‐MB‐231. Potential usefulness of these analogs as diagnostic imaging agents was assessed by biodistribution and imaging studies and compare with 99mTc‐BS.In view of these results, 99mTc‐BA1 and 99mTc‐BA2 were efficient radiotracer for targeting GRP receptor positive tumor than 99mTc‐BS. The 99mTc‐BA1 exhibited two different entities: specific for extra and an intracellular target in the same radioconjugate which seems to be a promising candidate for detection and therapy of GRP receptor positive lesions in the clinical phase. However, during scintigraphic studies 99mTC‐BA1 showed improved and distinct delineation of the tumor than 99mTC‐BA2 and 99mTC‐BS.These studies demonstrate the potential of using the bombesin analog, BA1 possessing antagonist C‐terminal vectors as a potential diagnostic as well as antagonistic agent for specific targeting of GRP‐receptors over‐expressing tumors. Abstract Increasing evidence of peptide receptor overexpression in various cancer cells, warrant the development of receptor specific radiolabeled peptides for molecular imaging and therapy in nuclear medicine. Gastrin‐releasing‐peptide (GRP) receptor, are overexpressed in a variety of human cancer cells. The present study report the synthesis and biological evaluation of new bombesin (BBN) analogs, HYNIC‐Asp‐[Phe13]BBN(7–13)‐NH‐CH2‐CH2‐CH3:BA1, HYNIC‐Pro‐[Tyr13Met14]BBN(7–14)NH2:BA2 as prospective tumor imaging agent with compare to BBN(7–14)NH2:BS as standard. The pharmacophores were radiolabeled in high yields with 99mTc, characterized for their stability in serum and saline, cysteine/histidine and were found to be substantially stable. Internalization/externalization and receptor binding studies were assessed using MDA‐MB‐231 cells and showed high receptor binding‐affinity and favourable internalization. Fluorescence studies revealed that BA1 changed the morphology of the cells and could localize in the nucleus more effectively than BA2/BS. Cell‐viability studies displayed substantial antagonistic and nuclear‐internalization effect of BA1. BA1 also exhibited antiproliferative effect on MDA‐MB‐231 cell by inducing apoptosis. In vivo behaviour of the radiopeptides was evaluated in GRP receptor positive tumor bearing mice. The 99mTc‐BA1/99mTc‐BA2 demonstrated rapid blood/urinary clearance through the renal pathway and comparatively more significant tumor uptake image and favourable tumor‐to‐non‐target ratios provided by 99mTc‐BA1. The specificity of the in vivo uptake was confirmed by co‐injection with BS. Moreover, 99mTc‐BA1 provided a much clearer tumor image in scintigraphic studies than others. Thus the combination of favourable in vitro and in vivo properties renders BA1 as more potential antagonist bombesin‐peptide for targeting GRP‐receptor positive tumor. These properties are encouraging to carry out further experiments for non‐invasive receptor targeting potential diagnostinc and therapeutic agent for tumors.

Metabolic stability and biological evaluation of 99mTc-HYNIC-Tyr3-Octreotide as somatostatin receptor positive tumor imaging agent

In this study, metabolic stability and biological evaluation of 99mTc labelled 6-hydrazinopyridine-3-carboxylic-acid (HYNIC)-Tyr3-Octreotide was reported as a candidate for imaging somatostatin-receptor (SSTR)-positive tumors. The metabolic stability analysis did not show any evidence of breaking of the labeled compound and formation of free 99mTc. In biodistribution and scintigraphy imaging study, radiopeptide have showed high and receptor-specific uptake in the SSTR2 positive organs, tumor with rapid renal excretion from non-target tissues, illustrating the excellent properties of this agent for SSTR tumor imaging.